Acute Myeloid leukaemia (AML) chemotherapy is linked to a considerable adverse drug reaction (ADRs). However, data regarding the ADRs in AML patients receiving chemotherapy in Kenya is scarce. This study aimed to assess the adverse drug reactions among AML patients treated at Kenyatta National Hospital (KNH).
Methods
A one-arm retrospective cohort study design was used to assess ADRs among eligible AML patients who received treatment at KNH between 1st January 2018 and 31st December 2023. A data abstraction tool was used to collect socio-demographics, comorbidities, the treatment regimen, and chemotherapy-related ADRs. The CTCAE v3.0 grading system and the modified Schumock and Thornton Scale were used to evaluate the severity and preventability of ADRs, respectively. The data collected was analysed using the SPSS version 29.0.01 software. Mean and median were used to report the age of participants, while other socio-demographic variables and adverse drug reactions were reported as percentages and frequencies.
Results
The prevalence of ADRs in this study was 96.7%, with a total of 123 ADRs recorded. The main adverse reactions observed were neutropenia (18%), thrombocytopenia (16.3%), anaemia (14.6%), and liver damage (10.6%). The majority of the ADRs recorded were of moderate severity (40.7%) and non-preventable (59.3%).
Conclusion
The prevalence of ADRs in AML patients was high. The most frequently reported ADR was neutropenia. The majority of ADRs were moderate severity level and non-preventable.
ZhouYHuangGCaiX, et al.Global, regional, and national burden of acute myeloid leukemia, 1990–2021: a systematic analysis for the global burden of disease study 2021. Biomark Res2024; 12: 101.
2.
HughesM. The global incidence and prevalence of acute myeloid leukemia over the next ten years (2017–2027). J Cancer Res Ther2017; 13: pS50
3.
KassahunWTesfayeGBimerewLG, et al.Prevalence of leukemia and associated factors among patients with abnormal hematological parameters in jimma medical center, southwest Ethiopia: a cross-sectional study. Adv Hematol2020; 2020: 1–7.
4.
LeakSAMmbagaLGMkwizuEW, et al.Hematological malignancies in east Africa—which cancers to expect and how to provide services. PLoS One2020; 15: e0232848.
5.
OkelloCDNiyonzimaNFerraressoM, et al.Haematological malignancies in sub-saharan Africa: east Africa as an example for improving care. Lancet Haematol2021; 8: e756–e769.
6.
WanjikuCMMellyBKilachC, et al.Acute myeloid leukemia in western Kenya: a snapshot. Blood2021; 138: 1223–1223.
7.
WangWZhangDLiangQ, et al.Global burden, risk factor analysis, and prediction study of leukaemia from 1990 to 2030. J Glob Health2024; 14: 04150.
8.
Meillon-GarciaLADemichelis-GómezR. Access to therapy for acute myeloid leukemia in the developing world: barriers and solutions. Curr Oncol Rep2020; 22: 125.
9.
Van WeelderenREKleinKNatawidjajaMD, et al.Outcome of pediatric acute myeloid leukemia (AML) in low- and middle-income countries: a systematic review of the literature. Expert Rev Anticancer Ther2021; 21: 765–780.
10.
EdwardsIRAronsonJK. Adverse drug reactions: definitions, diagnosis, and management. Lancet2000; 356: 1255–1259.
11.
LouëtLPittsHJP. Twenty-First century global ADR management: a need for clarification, redesign, and coordinated action. Ther Innov Regul Sci2023; 57: 100–103.
12.
AngamoMTChalmersLCurtainCM,et al.Adverse-Drug-Reaction-Related hospitalisations in developed and developing countries: a review of prevalence and contributing factors. Drug Saf2016; 39: 847–857.
13.
AmpaduHHHoekmanJde BruinML, et al.Adverse drug reaction reporting in Africa and a comparison of individual case safety report characteristics between Africa and the rest of the world: analyses of spontaneous reports in VigiBase®. Drug Saf2016; 39: 335–345.
14.
DöhnerHWeiAHAppelbaumFR, et al.Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood2022; 140: 1345–1377.
15.
CabreroMJabbourERavandiF, et al.Discontinuation of hypomethylating agent therapy in patients with myelodysplastic syndromes or acute myelogenous leukemia in complete remission or partial response: retrospective analysis of survival after long-term follow-up. Leuk Res2015 May; 39: 520–524.
16.
CrestanDTrojniakMPFrancesconS, et al.Pharmacovigilance of anti-cancer medicines: opportunities and challenges. Expert Opin Drug Saf2020 Jul 2; 19: 849–860.
17.
BarryAOlssonSMinziO, et al.Comparative assessment of the national pharmacovigilance systems in east Africa: Ethiopia, Kenya, Rwanda and Tanzania. Drug Saf2020; 43: 339–350.
18.
ObonyoCA. Health provider factors associated with reporting of adverse drug reactions in Kenyatta national hospital. Nairobi, Kenya: University of Nairobi, 2011.
19.
TrottiAColevasASetserA, et al.CTCAE V3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol2003 Jul; 13: 176–181.
20.
SchumockGTThorntonJP. Focusing on the preventability of adverse drug reactions. Hosp Pharm1992; 27: 538.
21.
RamasubbuSKPasrichaRKNathUK,et al.Frequency, nature, severity and preventability of adverse drug reactions arising from cancer chemotherapy in a teaching hospital. J Family Med Prim Care2020; 9: 3349.
22.
NagelGWeberDFrommE, et al.Epidemiological, genetic, and clinical characterization by age of newly diagnosed acute myeloid leukemia based on an academic population-based registry study (AMLSG BiO). Ann Hematol2017; 96: 1993–2003.
23.
ShallisRMWangRDavidoffA, et al.Epidemiology of acute myeloid leukemia: recent progress and enduring challenges. Blood Rev2019; 36: 70–87.
24.
TurbevilleSFrancisKMBehmI, et al.Prevalence and incidence of acute myeloid leukemia may be higher than currently accepted estimates among the ≥65 year-old population in the United States. Blood2014; 124: 958–958.
25.
LiuH. Emerging agents and regimens for AML. J Hematol Oncol2021 Dec 23; 14: 49.
26.
GriffithsEACarrawayHEChandhokNS,et al.Advances in non-intensive chemotherapy treatment options for adults diagnosed with acute myeloid leukemia. Leuk Res [Internet]2020; 91: 106339. https://linkinghub.elsevier.com/retrieve/pii/S0145212620300448. Available from:.
27.
UrbinoISecretoCOliviM, et al.Evolving therapeutic approaches for older patients with acute myeloid leukemia in 2021. Cancers (Basel)2021; 13: 5075.
28.
TzoganiKPenttiläKLapveteläinenT, et al.EMA Review of daunorubicin and cytarabine encapsulated in liposomes (vyxeos, CPX-351) for the treatment of adults with newly diagnosed, therapy-related acute myeloid leukemia or acute myeloid leukemia with myelodysplasia-related changes. Oncologist2020 Sep 1; 25: e1414–e1420.
29.
KaminskasEFarrellATWangYC, et al.FDA Drug approval summary: azacitidine (5-azacytidine, VidazaTM) for injectable suspension. Oncologist2005; 10: 176–182.
30.
Vargas NeriJLCastelán MartínezODCastañeda HernándezG, et al.Adverse drug reactions associated with anthracyclinebased chemotherapy in Mexican cancer pediatric patients: cohort study. Lat Am J Clin Sci Med Technol2020; 2: 9–17.
31.
KraussACGaoXLiL, et al.FDA Approval summary: (daunorubicin and cytarabine) liposome for injection for the treatment of adults with high-risk acute myeloid leukemia. Clin Cancer Res2019; 25: 2685–2690.
32.
LaiCDoucetteKNorsworthyK. Recent drug approvals for acute myeloid leukemia. J Hematol Oncol2019; 12: 100.
33.
OkikioluJDillonRRajK. Acute leukaemia. Medicine (Baltimore)2021; 49: 274–281.
34.
DovalDKumar SharmaSKumarM, et al.Cytarabine ears – A side effect of cytarabine therapy. J Oncol Pharm Pract2020; 26: 471–473.
35.
DuYLiCYanJ. The efficacy and safety of venetoclax and azacytidine combination treatment in patients with acute myeloid leukemia and myelodysplastic syndrome: systematic review and meta-analysis. Hematology2023; 28: 2198098.
36.
GozzoLVetroCBrancatiS, et al.Off-Label use of venetoclax in patients with acute myeloid leukemia: single center experience and data from pharmacovigilance database. Front Pharmacol2021; 12: 748766.
37.
YangYShuYChenG, et al.A real-world pharmacovigilance study of FDA adverse event reporting system (FAERS) events for venetoclax. PLoS One2022; 17: e0278725.
38.
Entezari-MalekiTMargedariSGholamiK, et al.Evaluation of chemotherapy toxicity in acute lymphoblastic and myelogenous leukemia. Int J Hematol Oncol Stem Cell Res2012; 6: 8–12.
39.
PhilipMSajNSebastianA, et al.Assessment of chemotherapy-induced febrile neutropenia in cancer patients. Indian J Med Paediatr Oncol2019; 40: 249–256.
